title: Conversion to everolimus in maintenance liver transplant patients: a multicenter, retrospective analysis.
abstract: Data on the conversion of patients to everolimus after liver transplantation are sparse. A multicenter, retrospective study followed 240 maintenance liver transplant patients to analyze the current indications for everolimus conversion, the employed regimens and exposure levels, and the impact on efficacy and safety. The mean time from transplantation to the introduction of everolimus was 4.9 ± 5.2 years. The mean everolimus trough level was 7.3 ± 4.1 ng/mL at month 1 and 8.1 ± 4.7 ng/mL at month 12. At 12 months, 61.6% of the patients were no longer receiving calcineurin inhibitor (CNI) therapy. The mean estimated glomerular filtration rate (eGFR) according to the Cockcroft-Gault formula was 64.2 ± 30.0 mL/minute on day 0 and 68.4 ± 32.5 mL/minute at month 12 (P = 0.007). Among patients with baseline serum creatinine levels ≥ 130 μmol/L, the eGFR values were 44.3 ± 15.7 mL/minute on day 0 and 53.7 ± 26.0 mL/minute at month 12 (P = 0.003). Four patients (1.6%) developed mild or moderate biopsy-proven acute rejection. Adverse events led to everolimus discontinuation in 12.9% of the patients. After the initiation of everolimus, the mean white blood cell count decreased significantly, and the total cholesterol and triglyceride levels increased significantly. In this retrospective analysis of the largest cohort of maintenance liver transplant patients analyzed after their conversion to everolimus, more than 60% of the patients were kept free of CNIs with a very low risk of acute rejection and with an acceptable safety profile. Randomized trials in which maintenance liver transplant patients are switched to everolimus in response to clinical indications or preemptively are warranted.
authors.affiliation: Centre Hépato-Biliaire, Hôpital Paul Brousse, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud, Villejuif, France. faouzi.saliba@pbr.aphp.fr
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dharancy
authors.forename: Richard
authors.initials: R
authors.lastname: Lorho
authors.forename: Filoména
authors.initials: F
authors.lastname: Conti
authors.forename: Sylvie
authors.initials: S
authors.lastname: Radenne
authors.forename: Martine
authors.initials: M
authors.lastname: Neau-Cransac
authors.forename: Monika
authors.initials: M
authors.lastname: Hurtova
authors.forename: Jean
authors.initials: J
authors.lastname: Hardwigsen
authors.forename: Yvon
authors.initials: Y
authors.lastname: Calmus
authors.forename: Jérome
authors.initials: J
authors.lastname: Dumortier
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D065095:Calcineurin Inhibitors; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D014280:Triglycerides; D000068338:Everolimus; D020123:Sirolimus